(SST15-05 ), 97th Scientific Assemble and Annual Meeting of the Radiological Society of North America (RSNA), December 2011 (talk)

Abstract

PURPOSE
Combined PET/MR imaging entails the use of MR contrast agents (MRCA) as part of integrated protocols. We assess additional attenuation of the PET emission signals in the presence of oral and intraveneous (iv) MRCA made up of iron oxide and Gd-chelates, respectively.
METHOD AND MATERIALS
Phantom scans were performed on a clinical PET/CT (Biograph HiRez16, Siemens) and integrated whole-body PET/MR (Biograph mMR, Siemens) using oral (Lumirem) and intraveneous (Gadovist) MRCA.
Reference PET attenuation values were determined on a small-animal PET (Inveon, Siemens) using standard PET transmission imaging (TX). Seven syringes of 5mL were filled with (a) Water, (b) Lumirem_100 (100% conc.), (c) Gadovist_100 (100%), (d) Gadovist_18 (18%), (e) Gadovist_02 (0.2%), (f) Imeron-400 CT iv-contrast (100%) and (g) Imeron-400 (2.4%). The same set of syringes was scanned on CT (Sensation16, Siemens) at 120kVp and 160mAs.
The effect of MRCA on the attenuation of PET emission data was evaluated using a 20cm cylinder filled uniformly with [18F]-FDG (FDG) in water (BGD). Three 4.5cm diameter cylinders were inserted into the phantom: (C1) Teflon, (C2) Water+FDG (2:1) and (C3) Lumirem_100+FDG (2:1). Two 50mL syringes filled with Gadovist_02+FDG (Sy1) and water+FDG (Sy2) were attached to the sides of (C1) to mimick the effects of iv-contrast in vessels near bone. Syringe-to-background activity ratio was 4-to-1. PET emission data were acquired for 10min each using the PET/CT and the PET/MR. Images were reconstructed using CT- and MR-based attenuation correction.
RESULTS
Mean linear PET attenuation (cm-1) on TX was (a) 0.098, (b) 0.098, (c) 0.300, (d) 0.134, (e) 0.095, (f) 0.397 and (g) 0.105. Corresponding CT attenuation (HU) was: (a) 5, (b) 14, (c) 3070, (d) 1040, (e) 13, (f) 3070 and (g) 347.
Lumirem had little effect on PET attenuation with (C3) being 13% and 10% higher than (C2) on PET/CT and PET/MR, respectively. Gadovist_02 had even smaller effects with (Sy1) being 2.5% lower than (Sy2) on PET/CT and 1.2% higher than (Sy2) on PET/MR.
CONCLUSION
MRCA in high and clinically relevant concentrations have attenuation values similar to that of CT contrast and water, respectively. In clinical PET/MR scenarios MRCA are not expected to lead to significant attenuation of the PET emission signals.

The interplay between optimization and machine learning is one of the most important developments in modern computational science. Optimization formulations and methods are proving to be vital in designing algorithms to extract essential knowledge from huge volumes of data. Machine learning, however, is not simply a consumer of optimization technology but a rapidly evolving field that is itself generating new optimization ideas. This book captures the state of the art of the interaction between optimization and machine learning in a way that is accessible to researchers in both fields.
Optimization approaches have enjoyed prominence in machine learning because of their wide applicability and attractive theoretical properties. The increasing complexity, size, and variety of today's machine learning models call for the reassessment of existing assumptions. This book starts the process of reassessment. It describes the resurgence in novel contexts of established frameworks such as first-order methods, stochastic approximations, convex relaxations, interior-point methods, and proximal methods. It also devotes attention to newer themes such as regularized optimization, robust optimization, gradient and subgradient methods, splitting techniques, and second-order methods. Many of these techniques draw inspiration from other fields, including operations research, theoretical computer science, and subfields of optimization. The book will enrich the ongoing cross-fertilization between the machine learning community and these other fields, and within the broader optimization community.

Combined whole-body PET/MR systems are being tested in clinical practice today. Integrated imaging protocols entail the use of MR contrast agents (MRCA) that could bias PET attenuation correction. In this work, we assess the effect of MRCA in PET/MR imaging. We analyze the effect of oral and intravenous MRCA on PET activity after attenuation correction. We conclude that in clinical scenarios, MRCA are not expected to lead to significant attenuation of PET signals, and that attenuation maps are not biased after the ingestion of adequate oral contrasts.

First clinical fully integrated whole-body PET/MR scanners are just entering the field. Here, we present studies toward quantification accuracy and variation within the PET field of view of small lesions from our BrainPET/MRI, a dedicated clinical brain scanner which was installed three years ago in Tbingen. Also, we present first results for patient and phantom scans of a fully integral whole-body PET/MRI, which was installed two months ago at our department. The quantification accuracy and homogeneity of the BrainPET-Insert (Siemens Medical Solutions, Germany) installed inside the magnet bore of a clinical 3T MRI scanner (Magnetom TIM Trio, Siemens Medical Solutions, Germany) was evaluated by using eight hollow spheres with inner diameters from 3.95 to 7.86 mm placed at different positions inside a homogeneous cylinder phantom with an 9:1 and 6:1 sphere to background ratio. The quantification accuracy for small lesions at different positions in the PET FoV shows a standard deviation of up to 11% and is acceptable for quantitative brain studies where the homogeneity of quantification on the entire FoV is essental. Image quality and resolution of the new Siemens whole-body PET/MR system (Biograph mMR, Siemens Medical Solutions, Germany) was evaluated according to the NEMA NU2 2007 protocol using a body phantom containing six spheres with inner diameter from 10 to 37 mm at sphere to background ratios of 8:1 and 4:1 and the F-18 point sources located at different positions inside the PET FoV, respectively. The evaluation of the whole-body PET/MR system reveals a good PET image quality and resolution comparable to state-of-the-art clinical PET/CT scanners. First images of patient studies carried out at the whole-body PET/MR are presented highlighting the potency of combined PET/MR imaging.

(OP314), Annual Congress of the European Association of Nuclear Medicine (EANM), October 2011 (talk)

Abstract

PURPOSE:Combined PET/MR imaging entails the use of MR contrast agents (MRCA) as part of integrated protocols. MRCA are made up of iron oxide and Gd-chelates for oral and intravenous (iv) application, respectively. We assess additional attenuation of the PET emission signals in the presence of oral and iv MRCA.MATERIALS AND METHODS:Phantom scans were performed on a clinical PET/CT (Biograph HiRez16, Siemens) and an integrated whole-body PET/MR (Biograph mMR, Siemens). Two common MRCA were evaluated: Lumirem (oral) and Gadovist (iv).Reference PET attenuation values were determined on a dedicated small-animal PET (Inveon, Siemens) using equivalent standard PET transmission source imaging (TX). Seven syringes of 5mL were filled with (a) Water, (b) Lumirem_100 (100% concentration), (c) Gadovist_100 (100%), (d) Gadovist_18 (18%), (e) Gadovist_02 (0.2%), (f) Imeron-400 CT iv-contrast (100%) and (g) Imeron-400 (2.4%). The same set of syringes was scanned on CT (Sensation16, Siemens) at 120kVp and 160mAs.The effect of MRCA on the attenuation of PET emission data was evaluated using a 20cm cylinder filled uniformly with [18F]-FDG (FDG) in water (BGD). Three 4.5cm diameter cylinders were inserted into the phantom: (C1) Teflon, (C2) Water+FDG (2:1) and (C3) Lumirem_100+FDG (2:1). Two 50mL syringes filled with Gadovist_02+FDG (Sy1) and water+FDG (Sy2) were attached to the sides of (C1) to mimick the effects of iv-contrast in vessels near bone. Syringe-to-background activity ratio was 4-to-1.PET emission data were acquired for 10min each using the PET/CT and the PET/MR. Images were reconstructed using CT- and MR-based attenuation correction (AC). Since Teflon is not correctly identified on MR, PET(/MR) data were reconstructed using MR-AC and CT-AC.RESULTS:Mean linear PET attenuation (cm-1) on TX was (a) 0.098, (b) 0.098, (c) 0.300, (d) 0.134, (e) 0.095, (f) 0.397 and (g) 0.105. Corresponding CT attenuation (HU) was: (a) 5, (b) 14, (c) 3070, (d) 1040, (e) 13, (f) 3070 and (g) 347.Lumirem had little effect on PET attenuation with (C3) being 13%, 10% and 11% higher than (C2) on PET/CT, PET/MR with MR-AC, and PET/MR with CT-AC, respectively. Gadovist_02 had even smaller effects with (Sy1) being 2.5% lower, 1.2% higher, and 3.5% lower than (Sy2) on PET/CT, PET/MR with MR-AC and PET/MR with CT-AC, respectively.CONCLUSION:MRCA in high and clinically relevant concentrations have attenuation values similar to that of CT contrast and water, respectively. In clinical PET/MR scenarios MRCA are not expected to lead to significant attenuation of the PET emission signals.

Hybrid imaging modalities such as [18F]FDG-PET/CT are superior in staging of e.g. lung cancer disease compared with stand-alone modalities. Clinical PET/MRI systems are about to enter the field of hybrid imaging and offer potential advantages. One added value could be a deeper insight into the tumor metabolism and tumorigenesis due to the combination of PET and dedicated MR methods such as MRS and DWI. Additionally, therapy monitoring of diffucult to diagnose disease such as chronic sclerodermic GvHD (csGvHD) can potentially be improved by this combination. We have applied PET/MRI in 3 patients with lung cancer and 4 patients with csGvHD before and during therapy. All 3 patients had lung cancer confirmed by histology (2 adenocarcinoma, 1 carcinoid). First, a [18F]FDG-PET/CT was performed with the following parameters: injected dose 351.7±25.1 MBq, uptake time 59.0±2.6 min, 3 min/bed. Subsequently, patients were brought to the PET/MRI imaging facility. The whole-body PET/MRI Biograph mMR system comprises 56 detector cassettes with a 59.4 cm transaxial and 25.8 cm axial FoV. The MRI is a modified Verio system with a magnet bore of 60 cm. The following parameters for PET acquisition were applied: uptake time 121.3±2.3 min, 3 bed positions, 6 min/bed. T1w, T2w, and DWI MR images were recorded simultaneously for each bed. Acquired PET data were reconstructed with an iterative 3D OSEM algorithm using 3 iterations and 21 subsets, Gaussian filter of 3 mm. The 4 patients with GvHD were brought to the brainPET/MRI imaging facility 2:10h-2:28h after tracer injection. A 9 min brainPET-acquisition with simultaneous MRI of the lower extremities was accomplished. MRI examination included T1-weighted (pre and post gadolinium) and T2-weighted sequences. Attenuation correction was calculated based on manual bone segmentation and thresholds for soft tissue, fat and air. Soleus muscle (m), crural fascia (f1) and posterior crural intermuscular septum fascia (f2) were surrounded with ROIs based on the pre-treatment T1-weighted images and coregistered using IRW (Siemens). Fascia-to-muscle ratios for PET (f/m), T1 contrast uptake (T1_post-contrast_f-pre-contrast_f/post-contrast_m-pre-contrast_m) and T2 (T2_f/m) were calculated. Both patients with adenocarcinoma show a lower ADC value compared with the carcinoid patient suggesting a higher cellularity. This is also reflected in FDG-PET with higher SUV values. Our initial results reveal that PET/MRI can provide complementary information for a profound tumor characterization and therapy monitoring. The high soft tissue contrast provided by MRI is valuable for the assessment of the fascial inflammation. While in the first patient FDG and contrast uptake as well as edema, represented by T2 signals, decreased with ongoing therapy, all parameters remained comparatively stable in the second patient. Contrary to expectations, an increase in FDG uptake of patient 3 and 4 was accompanied by an increase of the T2 signals, but a decrease in contrast uptake. These initial results suggest that PET/MRI provides complementary information of the complex disease mechanisms in fibrosing disorders.

We develop a novel method for detection of signals and reconstruction of images in the presence of random noise. The method uses results from percolation theory. We specifically address the problem of detection of multiple objects of unknown shapes in the case of nonparametric noise. The noise density is unknown and can be heavy-tailed. The objects of interest have unknown varying intensities. No boundary shape constraints are imposed on the objects, only a set of weak bulk conditions is required. We view the object detection problem as hypothesis testing for discrete statistical inverse problems. We present an algorithm that allows to detect greyscale objects of various shapes in noisy images. We prove results on consistency and algorithmic complexity of our procedures. Applications to cryo-electron microscopy are presented.

Combinatorial problems with submodular cost functions have recently drawn interest. In a standard combinatorial problem, the sum-of-weights cost is replaced by a submodular set function. The result is a powerful model that is though very hard. In this talk, I will introduce cooperative cuts, minimum cuts with submodular edge weights. I will outline methods to approximately solve this problem, and show an application in computer vision. If time permits, the talk will also sketch regret-minimizing online algorithms for submodular-cost combinatorial problems. This is joint work with Jeff Bilmes (University of Washington).

We propose two statistical tests to determine if two samples are
from different distributions. Our test statistic is in both cases
the distance between the means of the two samples mapped into a
reproducing kernel Hilbert space (RKHS). The first test is based on
a large deviation bound for the test statistic, while the second is
based on the asymptotic distribution of this statistic. We show that
the test statistic can be computed in $O(m^2)$ time. We apply our
approach to a variety of problems, including attribute matching for
databases using the Hungarian marriage method, where our test performs strongly.
We also demonstrate excellent
performance when comparing distributions over graphs, for which no
alternative tests currently exist.

NIPS Workshop on New Problems and Methods in Computational Biology, December 2006 (talk)

Abstract

We propose a new boosting method that systematically combines graph mining and mathematical programming-based machine learning. Informative and interpretable subgraph features are greedily found by a series of graph mining calls. Due to our mathematical programming formulation, subgraph features and pre-calculated real-valued features are seemlessly integrated. We tested our algorithm on a quantitative structure-activity relationship (QSAR) problem, which is basically a regression problem when given a set of chemical compounds. In benchmark experiments, the prediction accuracy of our method favorably compared with the best results reported on each dataset.

NIPS Workshop on Causality and Feature Selection, December 2006 (talk)

Abstract

We propose a new approach to infer the causal structure that has generated the observed statistical dependences among n random variables. The idea is that the factorization of the joint measure of cause and effect into P(cause)P(effect|cause) leads typically to simpler conditionals than non-causal factorizations. To evaluate the complexity of the conditionals we have tried two methods. First, we have compared them to those which maximize the conditional entropy subject to the observed first and second moments since we consider the latter as the simplest conditionals. Second, we have fitted the data with conditional probability measures being exponents of functions in an RKHS space and defined the complexity by a Hilbert-space semi-norm. Such a complexity measure has several properties that are useful for our purpose. We describe some encouraging results with both methods applied to real-world data. Moreover, we have combined constraint-based approaches to causal discovery (i.e., methods using only information
on conditional statistical dependences) with our method in order to distinguish between causal hypotheses which are equivalent with respect to the imposed independences. Furthermore, we compare the performance to Bayesian approaches to causal inference.

A promising new combination in multimodality imaging is MR-PET, where the high soft tissue contrast of Magnetic Resonance Imaging (MRI) and the functional information of Positron Emission Tomography (PET) are combined.
Although many technical problems have recently been solved, it is still an open problem to determine the attenuation map from the available MR scan, as the MR intensities are not directly related to the attenuation values. One standard approach is an atlas registration where the atlas MR image is aligned with the patient MR thus also yielding an attenuation image for the patient. We also propose another approach, which to our knowledge has not been tried before: Using Support Vector Machines we predict the attenuation value directly from the local image information. We train this well-established machine learning algorithm using small image patches.
Although both approaches sometimes yielded acceptable results, they also showed their specific shortcomings: The registration often fails with large deformations whereas the prediction approach is problematic when the local image structure is not characteristic enough. However, the failures often do not coincide and integration of both information sources is promising. We therefore developed a combination method extending Support Vector Machines to use not only local image structure but also atlas registered coordinates.
We demonstrate the strength of this combination approach on a number of examples.

After introducing the semi-supervised support vector machine (aka TSVM for "transductive SVM"), a few popular training strategies are briefly presented. Then the assumptions underlying semi-supervised learning are reviewed. Finally, two modern TSVM optimization techniques are applied to the spam filtering data sets of the workshop; it is shown that they can achieve excellent results, if the problem of the data being non-iid can be handled properly.

In the field of machine learning, semi-supervised learning (SSL) occupies the middle ground, between supervised learning (in which all training examples are labeled) and unsupervised learning (in which no label data are given). Interest in SSL has increased in recent years, particularly because of application domains in which unlabeled data are plentiful, such as images, text, and bioinformatics. This first comprehensive overview of SSL presents state-of-the-art algorithms, a taxonomy of the field, selected applications, benchmark experiments, and perspectives on ongoing and future research.
Semi-Supervised Learning first presents the key assumptions and ideas underlying the field: smoothness, cluster or low-density separation, manifold structure, and transduction. The core of the book is the presentation of SSL methods, organized according to algorithmic strategies. After an examination of generative models, the book describes algorithms that implement the low-density separation assumption, graph-based methods, and algorithms that perform two-step learning. The book then discusses SSL applications and offers guidelines for SSL practitioners by analyzing the results of extensive benchmark experiments. Finally, the book looks at interesting directions for SSL research. The book closes with a discussion of the relationship between semi-supervised learning and transduction.

Analyzing resequencing array data using machine learning, we obtain a genome-wide inventory of
polymorphisms in 20 wild strains of Arabidopsis thaliana, including 750,000 single nucleotide poly-
morphisms (SNPs) and thousands of highly polymorphic regions and deletions. We thus provide an
unprecedented resource for the study of natural variation in plants.

We compare the predictive accuracy of the Dirichlet Process Gaussian mixture models using conjugate and conditionally conjugate priors and show that better density models result from using the wider class of priors. We explore several MCMC schemes exploiting conditional conjugacy and show their computational merits on several multidimensional density estimation problems.

Latent variable models are powerful tools to model the underlying structure in
data. Infinite latent variable models can be defined using Bayesian nonparametrics.
Dirichlet process (DP) models constitute an example of infinite latent class models
in which each object is assumed to belong to one of the, mutually exclusive, infinitely
many classes. Recently, the Indian buffet process (IBP) has been defined as
an extension of the DP. IBP is a distribution over sparse binary matrices with infinitely
many columns which can be used as a distribution for non-exclusive features.
Inference using Markov chain Monte Carlo (MCMC) in conjugate IBP models has
been previously described, however requiring conjugacy restricts the use of IBP. We
describe an MCMC algorithm for non-conjugate IBP models.
Modelling the choice behaviour is an important topic in psychology, economics
and related fields. Elimination by Aspects (EBA) is a choice model that assumes
each alternative has latent features with associated weights that lead to the observed
choice outcomes. We formulate a non-parametric version of EBA by using IBP as
the prior over the latent binary features. We infer the features of objects that lead
to the choice data by using our sampling scheme for inference.

17th International Conference on Arabidopsis Research, April 2006 (talk)

Abstract

We have used high-density oligonucleotide arrays to characterize common sequence variation in 20 wild strains of Arabidopsis thaliana that were chosen for maximal genetic diversity. Both strands of each possible SNP of the 119 Mb reference genome were represented on the arrays, which were hybridized with whole genome, isothermally amplified DNA to minimize ascertainment biases. Using two complementary approaches, a model based algorithm, and a newly developed machine learning method, we identified over 550,000 SNPs with a false discovery rate of ~ 0.03 (average of 1 SNP for every 216 bp of the genome). A heuristic algorithm predicted in addition ~700 highly polymorphic or deleted regions per accession. Over 700 predicted polymorphisms with major functional effects (e.g., premature stop codons, or deletions of coding sequence) were validated by dideoxy sequencing. Using this data set, we provide the first systematic description of the types of genes that harbor major effect polymorphisms in natural populations
at moderate allele frequencies. The data also provide an unprecedented resource for the study of genetic variation in an experimentally tractable, multicellular model organism.

Gaussian processes (GPs) provide a principled, practical, probabilistic approach to learning in kernel machines. GPs have received increased attention in the machine-learning community over the past decade, and this book provides a long-needed systematic and unified treatment of theoretical and practical aspects of GPs in machine learning. The treatment is comprehensive and self-contained, targeted at researchers and students in machine learning and applied statistics.
The book deals with the supervised-learning problem for both regression and classification, and includes detailed algorithms. A wide variety of covariance (kernel) functions are presented and their properties discussed. Model selection is discussed both from a Bayesian and a classical perspective. Many connections to other well-known techniques from machine learning and statistics are discussed, including support-vector machines, neural networks, splines, regularization networks, relevance vector machines and others. Theoretical issues including learning curves and the PAC-Bayesian framework are treated, and several approximation methods for learning with large datasets are discussed. The book contains illustrative examples and exercises, and code and datasets are available on the Web. Appendixes provide mathematical background and a discussion of Gaussian Markov processes.

The 22nd International Conference on Machine Learning, August 2005 (talk)

Abstract

We propose a general framework for learning from labeled and unlabeled data on a directed graph in which the structure of the graph including the directionality of the edges is considered. The time complexity of the algorithm derived from this framework is nearly linear due to recently developed numerical techniques. In the absence of labeled instances, this framework can be utilized as a spectral clustering method for directed graphs, which generalizes the spectral clustering approach for undirected graphs. We have applied our framework to real-world web classification problems and obtained encouraging results.

We discuss reproducing kernel Hilbert space (RKHS)-based measures of statistical dependence,
with emphasis on constrained covariance (COCO), a novel criterion to
test dependence of random variables. We show that COCO is a test for independence if and only if the associated RKHSs
are universal.
That said, no independence
test exists that can distinguish dependent and independent random variables in all circumstances. Dependent random variables can result in a COCO which is arbitrarily close to zero when the source densities are highly non-smooth. All current kernel-based independence tests share this behaviour. We demonstrate exponential convergence between the population and empirical COCO. Finally, we use COCO as a measure of joint neural activity between voxels in MRI recordings of the macaque monkey, and compare the results to the mutual information and the correlation. We also show the effect of removing breathing artefacts from the MRI recording.

Using robots as models of cognitive behaviour has a long tradition in robotics. Parallel to the historical development in cognitive science, one observes two major, subsequent waves in cognitive robotics. The first is based on ideas of classical, cognitivist Artificial Intelligence (AI). According to the AI view of cognition as rule-based symbol manipulation, these robots typically try to extract symbolic descriptions of the environment from their sensors that are used to update a common, global world representation from which, in turn, the next action of the robot is derived. The AI approach has been successful in strongly restricted and controlled environments requiring well-defined tasks, e.g. in industrial assembly lines.
AI-based robots mostly failed, however, in the unpredictable and unstructured environments that have to be faced by mobile robots. This has provoked the second wave in cognitive robotics which tries to achieve cognitive behaviour as an emergent property from the interaction of simple, low-level modules. Robots of the second wave are called animats as their architecture is designed to closely model aspects of real animals. Using only simple reactive mechanisms and Hebbian-type or evolutionary learning, the resulting animats often outperformed the highly complex AI-based robots in tasks such as obstacle avoidance, corridor following etc.
While successful in generating robust, insect-like behaviour, typical animats are limited to stereotyped, fixed stimulus-response associations. If one adopts the view that cognition requires a flexible, goal-dependent choice of behaviours and planning capabilities (H.A. Mallot, Kognitionswissenschaft, 1999, 40-48) then it appears that cognitive behaviour cannot emerge from a collection of purely reactive modules. It rather requires environmentally decoupled structures that work without directly engaging the actions that it is concerned with. This poses the current challenge to cognitive robotics: How can we build cognitive robots that show the robustness and the learning capabilities of animats without falling back into the representational paradigm of AI?
The speakers of the symposium present their approaches to this question in the context of robot navigation and sensorimotor learning. In the first talk, Prof. Helge Ritter introduces a robot system for imitation learning capable of exploring various alternatives in simulation before actually performing a task. The second speaker, Angelo Arleo, develops a model of spatial memory in rat navigation based on his electrophysiological experiments. He validates the model on a mobile robot which, in some navigation tasks, shows a performance comparable to that of the real rat. A similar model of spatial memory is used to investigate the mechanisms of territory formation in a series of robot experiments presented by Prof. Hanspeter Mallot. In the last talk, we return to the domain of sensorimotor learning where Ralf M{\"o}ller introduces his approach to generate anticipatory behaviour by learning forward models of sensorimotor relationships.

Our goal is to understand the principles of Perception, Action and Learning in autonomous systems that successfully interact with complex environments and to use this understanding to design future systems